Potassium Hydroxide → HCID 68485824, compound

HRID 1401646Notes

Reaction equation

HRID 1401646 reaction equation
S(Cl)(Cl)=O.[CH3:5][N:6]1[CH2:33][CH2:32][C:9]2[N:10]([CH2:18][C:19]([C:22]3[CH:31]=[CH:30][C:25]([C:26]([NH:28][CH3:29])=[O:27])=[CH:24][CH:23]=3)(O)[CH3:20])[C:11]3[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][C:16]=3[C:8]=2[CH2:7]1.[OH-].[K+]>CN1C(=O)CCC1.O>[CH3:5][N:6]1[CH2:33][CH2:32][C:9]2[N:10]([CH:18]=[C:19]([C:22]3[CH:23]=[CH:24][C:25]([C:26]([NH:28][CH3:29])=[O:27])=[CH:30][CH:31]=3)[CH3:20])[C:11]3[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][C:16]=3[C:8]=2[CH2:7]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 24386Thionyl ChlorideHCID 67304341HCID 67304341, compound

Product 1

HCID 68485824HCID 68485824, compoundYield 4.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Thionyl chloride (1.5 mL, 20.67 mmol) was added to a solution of 4-[2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-hydroxy-1-methyl-ethyl]-N-methyl-benzamide (130 mg, 0.33 mmol) and the reaction mixture stirred at RT for 30 min. The solvent was removed under vacuum to obtain the crude as a foamy solid, which was dissolved in NMP (3 mL). The reaction mixture was stirred for 5 min. Powdered KOH (186 mg, 3.32 mmol) was added and the contents heated at 80° C. for 20 min. After completion of reaction, the reaction mixture was poured in water and the desired compound extracted with EtOAc (3×40 mL). The organic layer was washed with water, concentrated under vacuum to obtain the crude product (100 mg) which was purified by reverse phase HPLC to yield 6.0 mg of 4-[2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1methyl-vinyl]-N-methyl-benzamide as the free base. 1H NMR (CDCl3, free base) δ (ppm): 7.78 (d, 2H), 7.58 (d, 2H), 7.22 (s, 1H), 7.05 (m, 2H), 6.96 (s, 1H), 6.20 (bs, 1H), 4.0 (s, 2H), 3.16 (m, 2H), 3.05 (d, 3H), 2.90 (m, 2H), 2.70 (s, 3H), 2.42 (s, 3H), 1.99 (s, 3H).

Workup

  1. customThe solvent was removed under vacuum
  2. customto obtain the crude as a foamy solid, which
  3. stirringThe reaction mixture was stirred for 5 min
  4. temperaturethe contents heated at 80° C. for 20 min
  5. customAfter completion of reaction
  6. extractionthe desired compound extracted with EtOAc (3×40 mL)
  7. washThe organic layer was washed with water
  8. concentrationconcentrated under vacuum
  9. customto obtain the crude product (100 mg) which
  10. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-70da91d9697e406c9c7291a7bff003d4
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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